colorectal cancer risk, chronic illnesses, operations, and … · ported by the "nicholas and...

(CANCER RESEARCH 48, 4399-4404, August I, 1988]

Colorectal Cancer Risk, Chronic Illnesses, Operations, and Medications: CaseControl Results from the Melbourne Colorectal Cancer Study1

Gabriel A. Kune,2 Susan Kune, and Lyndsey F. Watson

Department of Surgery, University of Melbourne, Repatriation General Hospital, Heidelberg 3081, Victoria, Australia

ABSTRACT

The associations between colorectal cancer risk and several chronicillnesses, operations, and various medications were examined in 715colorectal cancer cases and 727 age/sex-matched controls in data derivedfrom a large, comprehensive, population-based study of this cancerconducted in Melbourne, Australia. There was a statistically significantdeficit among cases of hypertension, heart disease, stroke, chronic chestdisease, and chronic arthritis and a statistically significant excess of"hemorrhoids" among cases, and all of these differences were consistent

for both colon and rectal cancer and for both males and females. Althoughno statistically significant differences were found for other cancers, therewere twice as many breast cancers among cases (16) than among controls(8) and also there were 9 uterine cancers among cases and only 2 amongcontrols. There was a statistically significant deficit among cases in theuse of aspirin-containing medication and vitamin supplements, and thiswas consistent for both colon and rectal cancer and for both males andfemales. There was a statistically significant excess of large bowelpolypectomy among cases. The modeling of these significant associationssimultaneously in a logistic regression equation indicated that hypertension, heart disease, chronic arthritis, and aspirin use were each independent effects and consistent for both colon and rectal cancer for both malesand females and also that these effects were independent of dietary riskfactors previously described in the Melbourne study. The possible relevance of these findings towards an understanding of colorectal cancerrisk and etiology is discussed.

INTRODUCTION

This paper describes the associations found between colorectal cancer risk and several chronic illnesses, operations, andmedications. The data are drawn from the case-control substudyarm of a large, comprehensive, population-based clinicopatho-logical and epidemiolÃ³gica! investigation of colorectal cancer,The Melbourne Colorectal Cancer Study ( 1). The objectives forobtaining these data on illnesses, operations, and medicationswere partly to examine some current hypotheses of colorectalcancer risk, partly to examine previously described associationsbetween colorectal cancer and other cancers and partly as anexploratory step to stimulate the creation of new hypotheses ofcolorectal cancer etiology.

PATIENTS AND METHODS

Definition of Cases and Controls. All histologically confirmed newcases of colorectal adenocarcinoma diagnosed in the 12-month periodApril 1980 to April 1981 who were usual residents of MetropolitanMelbourne (population, 2.81 million) constituted the cases (1-3). Thosewith a past history of ulcerative colitis or familial polyposis coli (10cases) were excluded. Community controls, who were age/sex frequencymatched with the cases, were randomly selected from the same geographic area from which the cases were chosen, according to a cluster-sampling plan devised by the Australian Bureau of Statistics (1, 2).

Received 5/4/87; revised 10/15/87, 4/11/88; accepted 4/27/88.The costs of publication of this article were defrayed in part by the payment

of page charges. This article must therefore be hereby marked advertisement inaccordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1This part of the Melbourne Colorectal Cancer Study was generously supported by the "Nicholas and Elizabeth Slezak Cancer Research Fund" of the

University of Melbourne.2To whom requests for reprints should be addressed.

There were 715 cases and 727 age/sex frequency-matched controlsavailable for this analysis.

Data Collection. Data were collected by two questionnaires, whichwere administered by personal interview, each on a separate occasionand by two different sets of interviewers. The first questionnaire included data on age, sex, country of birth, and religion; current and pastillnesses, operations, and medications; bowel habit; biopsychosocialfactors; number of children; and family history data. The second interview was the dietary questionnaire, which included alcohol intake andtobacco use. The section of the interview which dealt with previousillnesses operations and medications was introduced uniformly by theinterviewer as follows: "I'd like to talk to you about your general health.

I am now going to read through a list of operations, illnesses, andmedications. Would you tell me if you have had any of these, and if so,when?" The responses were recorded as "yes," "no," or "don't know."

For operations, the actual year of the procedure was recorded. For theillnesses, the year of commencement and the year of termination of theillness was recorded. For medications, the frequency was recorded as"daily," "weekly," or "don't know" and the duration was recorded from

commencement year to termination year of medication. The dataobtained were not verified by any other means, such as by checkingphysician or hospital records or by interviewing close relatives orfriends. The chronic illnesses which were asked are listed in Table 1,the cancers (other than colorectal cancer) in Table 2, the medicationsin Table 3, and the operations in Table 4.

Data Analysis. Data manipulations and cross-tabulations were madeusing SPSS-x (4). The analysis of the associations between the variousillnesses, operations, and medications and colorectal cancer was doneusing the GLIM statistical package (5) to carry out unconditionallogistic regression (6), which gives multiplicative models for the KKof being a case. Design constraints, namely age and sex (due to frequency matching between cases and controls), were adjusted for in alllogistic regression models.

Preliminary assessment of these associations was done univariatelyfor colon and rectal cancers as well as for colorectal cancer (colon andrectum combined). Possible sex differences were also tested for. Simultaneous assessment of significant variables was then done and a muli i-variate model was developed and tested for consistency across site andsex and also with simultaneous adjustment for a dietary model of riskpreviously developed for this data set (7).

RESULTS

This analysis is of 715 cases (388 males and 327 females)and 727 controls (398 males and 329 females). There were 392colon cancers and 323 rectal cancers among the cases. Casesand controls were group matched for age and sex, and the ageand sex distribution of the cases and controls was thereforesimilar, with a mean age of 65 years (standard deviation of 10for males and 12 for females).

Univariate Analyses of Associations

Illnesses. Table 1 summarizes the chronic illnesses findings.There was a statistically significant deficit among cases ofhypertension, stroke, heart disease, chronic chest disease, andchronic arthritis, and these deficits were consistent in bothcolon and rectal cancer and in both males and females. Amongcases, there was a statistically significant excess of "hemor-

' The abbreviation used is: RR, relative risk.

4399

on March 3, 2020. © 1988 American Association for Cancer Research. cancerres.aacrjournals.org Downloaded from

http://cancerres.aacrjournals.org/

COLORECTAL CANCER RISK

Table I Distribution of chronic illnesses among cases and controls and relative risk estimates

Males(cases, n = 388;

controls, n =398)IllnessHypertensionStrokeHeart

diseaseChest

diseaseAsthmaArthritisDiabetesIndigestion

orulcerDiverticulitisHemorrhoidsNervousness

ornervousbreakdownAllergies

orhayfeverStatusCase

ControlCase

ControlCase

ControlCase

ControlCase

ControlCaseControlCase

ControlCase

ControlCase

ControlCase

ControlCase

ControlCaseControlNo.

withillness113

149132572

10661

8628

3011817521

17166

14821

14138

1136362110134RR0.690.520.630.680.950.561.281.261.571.391.050.78CIÂ°

P0.51-0.93

0.020.26-1.

U30.080.45-0.88

0.0080.47-0.97

0.040.56-1.63

0.990.42-0.75

<0.0010.67-2.47

0.60.95-1.68

0.120.79-3.13

0.31.03-1.88

0.040.72-1.54

0.90.58-1.06

0.12No.

withillness114

1348

1849

6643522025151

18312

1693

12326

21114

6488

71128139Females

(cases, n = 326;controls, n =329)RR0.780.430.700.810.790.690.750.671.272.231.340.88CI

P0.57-1.08

0.150.19-1.01

0.080.47-1.06

0.110.52-1.25

0.40.43-1.47

0.60.51-0.93

0.020.35-1.61

0.60.48-0.93

0.020.70-2.32

0.51.56-3.23

<0.0010.93-1.92

0.120.65-1.20

0.5No.

withillness227

28321

43121

172104

13848

55269

35833

33259

27147

35252177151

133238273Total

(cases, n = 714;controls, n =727)RR0.730.480.660.730.890.621.020.961.391.691.200.83CI0.59-0.910.28-0.820.51-0.850.55-0.960.60-1.330.51-0.770.62-1.670.78-1.190.88-2.171.35-2.130.93-1.560.67-1.03P0.0050.0090.0020.030.6<0.0010.990.70.18<0.0010.190.10"

CI, 95% confidence interval.Table

2 Distribution of cancers, other than colorectal cancer, among cases and controls and their relativeriskMales

(cases, n = 388;controls, n =398)Excision

forskincancerMastectomy

forcancerHysterectomy

foruterinecancerProstatic

surgeryforcancerCancer

in othersitesStatusCase



ControlNo.Yes

DK"RR42

243451

0001

274 31.300.25CI

P0.81-2.09

0.30.4No.Yes

DK18

1524615

0809

172 8Females

(cases, n = 327;controls, n =329)RR0.741.934.63CI

P0.39-1.39

0.40.81-4.61

0.20.99-21.6

0.07No.Yes

DK60

39581116

0807

010 0estimatesTotal

(cases, n = 715;controls, n =727)RR1.062.060.71CI0.72-1.540.87-4.840.27-1.87P0.80.140.7

" DK, don't know. All "don't know" responses considered for relative risk estimation to be nonmalignant; CI, 95% confidence interval.

rhoids" in both colon and rectal cancers. There was a statistically significant deficit of "indigestion or ulcer" reported by

female cases, and this was similar for both colon and rectalcancer. No differences were found for asthma, diabetes, diver-ticular disease, "extreme nervousness and nervous breakdowns," and allergies.

A past history of cancers other than colorectal cancer wasseen in 85 cases and 75 controls, there being 92 instances incases and 82 in controls (Table 2). Note that a past history ofcolorectal cancer was an exclusion for controls. For operations,all the "don't know" responses were in relation to malignant or

premalignant conditions and were distributed as follows: bowel

polypectomy, 16 cases and no controls; gastric cancer surgery,2 cases and no controls; prostatic cancer surgery, 27 cases and3 controls; uterine cancer surgery, 17 cases and 8 controls; skincancer surgery, 39 cases and 11 controls. Thus the 123 "don'tknow" answers were distributed among cases in 101 instances

and among controls in 22 instances. The distribution of cancersites among cases and controls is described in Table 2, and inthis table, for relative risk estimates, all "don't know" responses

were considered to be nonmalignant. There were no statisticallysignificant differences either in the total number of other cancers, nor in any one site, and the rates were similar for colonand rectal cancer. It is noteworthy that there were twice as

4400




many breast cancers among cases than among controls. Thedifference for uterine cancer was approaching statistical significance at the 5% level (P = 0.07; Table 2). Note that in thequestion on hysterectomy for uterine cancer, no distinction wasmade in the questionnaire between endometrial cancer andcervical cancer.

Medications. With past medications (Table 3) there was astatistically significant deficit among cases consuming aspirinand aspirin-containing medications, retinol supplements, andvitamin C supplements, and these deficits were consistent formales and females. The statistically significant lower consumption of aspirin and aspirin-containing medications among casesremained after adjustment was made for those with arthritis,who may be supposed to be frequent users of aspirin-containingcompounds (P < 0.001; RR = 0.63; 95% confidence interval,0.50-0.78). The use of nonsteroidal antiinflammatory agents,steroids, oral contraceptives, sedatives, tranquilizers, and sleeping pills was similar for cases and controls and consistent formales and females, colon and rectal cancer combined (Table 3).When these groups of medications were analyzed by site (coloncancer and rectal cancer), the effects noted above were unalteredwith the exception of nonsteroidal antiinflammatory agents,where a deficit was noted for colon cancer cases (RR = 0.66;95% confidence interval, 0.47-0.92; P = 0.001) and this wasconsistent for both males and females.

Operations. A history of a previous bowel polypectomyshowed a statistically significant excess in cases and there wasalso a statistically significant deficit of cases who had uterinecurettage (Table 4). The rates of tonsillectomy, appendectomy,hemorrhoidectomy, cholecystectomy, hernia repair, hiatus hernia repair, peptic ulcer surgery, hysterectomy for nonmalignantlesions, breast lumpectomy, and prostatic surgery for nonmalignant lesions showed no statistically significant differencesbetween cases and controls, colon and rectal cancer combined(Table 4).

When these operations were analyzed by site (colon cancerand rectal cancer) the effects seen above were unaltered, with

the exception of breast lumpectomy, where the deficit was seenonly in colon cancer cases (RR = 0.22; confidence interval,0.06-0.78; P = 0.02). The numbers in this last subset were verysmall (3 cases and 14 controls).

Multivariate Modeling of Significant Associations

The illnesses and medications which were consistently statistically significantly associated with the risk of colorectal cancerin the univariate analysis were considered simultaneously in alogistic regression equation. The illnesses considered in thisequation were hypertension, stroke, heart disease, chronic chestdisease, and chronic arthritis and aspirin use. Although"hemorrhoids" were associated with the risk of colorectal can

cer, this variable was not included because of the considerationthat "hemorrhoid" symptomatology is likely to be confounded

with that of colorectal cancer. Also vitamin supplements werenot included in the modeling, because they form part of thedietary risk model, described below.

Chronic chest disease was removed from this equation because the P value associated with its inclusion was only 0.13.The resulting equation showed that both hypertension andstroke were only marginally significant (P = 0.07 and P = 0.06,respectively). The number reporting stroke was small (Table 1)and its effect compared with that of hypertension was considered to have less power; therefore stroke was excluded from themodel at this stage. The model then included hypertension,heart disease, chronic arthritis, and aspirin use and was considered to be an adequate explanation of the associations found.These results were consistent across sex and site (colon andrectum) although less statistically powerful in the rectum (Table5).

In the dietary part of the Melbourne study, a model of dietaryrisk factors was created. The dietary factors were highly statistically significantly associated with colorectal cancer risk (7)(deviance change approximated by xn2 = 212, P < 0.001).

These risk factors were: low intake of dietary fiber vegetables,

Table 3 Distribution of medication use among cases and controls and relative risk estimates

MedicationAspirin

andaspirincontainingNonsteroid

anti-inflammatoriesSteroidsOral

contraceptivesTranquilizers

andsedativesSleeping

pillsVitamin

supplementsRetinolVitamin

CStatusCaseControlCase


ControlCase

ControlCase

ControlCase

ControlCase

ControlMales

(cases, n = 388;controls, n =398)No.

using RR CI*P4167

0.58 0.38-0.880.02iU

0.80 0.56-1.160.323

1.69 0.83-3.450.2g*

0.86 0.58-1.280.5^

0.96 0.62-1.470.92g

0.28 0.13-0.630.024Â°

0.42 0.24-0.72 0.02Females

(cases, n = 325Â°;controls, n =329)No.

using RRCI4480

0.490.32-0.73*Â¿

0.740.51-1.0930

0.940.55-1.613Ã§

1.260.80-2.0H*

0.980.67-1.4373

0.720.49-1.0624

0.160.05-0.46^

0.24 0.12-0.45Total

(cases, n â€”713;controls, n =727)No.

/' using RRCI85<0.001

147 0.530.40-0.710.1

Â¡33 0.770.60-1.010.9

43 1.170.77-1.790.40.99

Â¡33 0.930.71-1.220.1

Â¡22 0.820.61-1.09<0.001

52 0.220.12-0.42<0.001

g2 Â°-32 0.21-0.49P<0.0010.060.50.60.2<0.001<0.001

" Two female cases with missing data excluded.* Cl, 95% confidence interval.

4401




Table 4 Distribution of previous operations, excluding cancer operations, among cases and controls and relative risk estimates

Males(cases, n = 388;

controls, n =398)OperationTonsillectomyAppendectomyHemorrhoidectomyChclecystectomyHernia

repairHiatus

herniarepairPeptic

ulcersurgeryBowel

poly-pectomy*Uterine

curettageHysterectomy

fornonmalignant

lesionBreast

lumpectomyProstatic

surgeryfor non-malignant lesionNo.

withprevious

Status operation RRCIÂ°Case

ControlCase

ControlCase

ControlCase

ControlCase

ControlCase

ControlCase

ControlCase

ControlCase

ControlCase

ControlCaseControlCaseControlÂ¡jp

0.930.70-1.25Si

*â€¢Â»^2'â€¢*17

. ,,14'-2687

11381:

1.03912'0

5.2430

40 0.750.70-1.390.83-2.170.61-20.81-10.32-1.56.59.821.14-250.46-1.23Females

(cases, n = 327;controls, n =329)No.

withprevious

P operationRR0.7

HI0.99

Â«0.3

Â¡30.7

4jÂ°-5

\\2

30.7

50.04

1474

9997

11914220.3"

CI, 95% confidence interval.'' Four male cases and 12 female cases with "don't know" responses excluded.c 26 cases and 10 controls with "operations for cancer" or "operations, don't know0.921.230.930.980.930.670.407.310.680.800.62ifcancerCI

P0.67-1.27

0.60.86-1.75

0.30.42-2.04

0.990.62-1.54

0.990.43-2.00

0.990.08-2.08

0.51.64-33

0.0050.48-0.96

0.040.57-1.11

0.110.31-1.25

0.2"

responses excluded.Total(cases,

n = 715;controls, n =727)No.

withprevious

operationRR257274169

16053

455957100

9534111724

40.931.101.211.061.080.760.656.28CI0.75-1.150.85-1.410.81-1.820.72-1.540.80-1.470.30-1.412.17-20P0.50.50.40.80.70.4Â«CO.OOITable

5 Model of illnesses and aspirin use, by site and sex, and with simultaneous adjustment for model of dietaryriskColorÃ©ela!

cancerMales + femalesMalesFemalesAfter adjustment for

dietfactorsColon

cancerMales -I-femalesMalesFemalesAfter adjustment for

dietfactorsRectal

cancerMales -1-femalesMalesFemalesAfter adjustment for

diet factorsRR0.80

0.760.840.790.74

0.710.760.750.89

0.820.970.87HypertensionCI"0.63-1.01

0.55-1.040.60-1.190.62-1.020.56-0.98

0.48-1.060.51-1.140.55-1.020.66-1.20

0.55-1.230.62-1.510.63-1.20P0.05

0.080.30.060.03

0.090.170.060.4

0.30.90.4RR0.73

0.700.780.760.73

0.720.750.720.73

0.680.810.76Heart

diseaseCI0.55-0.97

0.49-1.000.50-1.210.56-1.030.52-1.03

0.46-1.120.44-1.260.50-1.030.51-1.06

0.43-1.090.45-1.450.52-1.13Chronic

arthritisP0.03

0.050.260.070.06

0.140.270.070.09

0.100.50.16RR

CI0.66

0.53-0.830.60 0.44-0.820.74 0.53-1.030.710.56-0.900.57

0.43-0.750.46 0.31-0.680.70 0.48-1.030.630.47-0.850.78

0.58-1.030.78 0.53-1.140.76 0.49-1.180.78 0.57-1.06P<0.001

<0.0010.06

0.004<0.001

<0.0010.060.0010.08

0.190.210.10RR0.60

0.720.520.570.57

0.610.550.530.64

0.830.490.59Aspirin

useCI0.44-0.82

0.46-1.120.34-0.800.41-0.790.39-0.83

0.34-1.100.33-0.910.35-0.800.43-0.95

0.48-1.420.27-0.870.39-0.91P<0.001

0.130.00

<0.0010.003

0.090.020.0010.02

0.50.01

0.01*

CI, 95% confidence interval.

cruciferous vegetables, dietary vitamin C, pork, fish, "othermeats" (as defined in the study), vitamin supplements, low or

high intake of milk drinks and high intake of fat, and, for malesonly, high intake of beef. These factors were fitted as possibleconfounders and did not explain the case-control differences

aspirin use. Similar effects were found when the data wereanalyzed by colon cancer and rectal cancer (Table 5).

DISCUSSION

In the univariate analysis the statistically significant deficitfound for hypertension, heart disease, chronic arthritis, and of hypertension, stroke, chronic chest disease, chronic arthritis,

4402




and aspirin use noted for cases is an interesting finding whichchallenges the cancer epidemiologist to generate new hypotheses of colorectal cancer etiology and risk. When all thesefactors were examined together in a logistic regression equation,the effects of stroke and chronic chest disease were very muchreduced and so were removed from the consequent etiologicalmodel. The authors had no a priori hypotheses regarding colorectal cancer and these factors.

Subsequent to these findings, diet was postulated to be thefactor explaining the case-control differences found with hypertension, heart disease, chronic arthritis, and aspirin use. Thiswas tested by fitting into a logistic regression model, simultaneously, the dietary risk factors (found in the Melbourne study(7) and described earlier under "Results") and the above ill

nesses and aspirin use. It was seen that the estimation of allthese effects were unchanged, and then it was concluded thatthe diet risk factors were independent of the above illnesses andaspirin use.

The highly statistically significant deficit of chronic arthritisamong cases applied to both males and females separately andwas not explained by dietary differences. It may be that thecontrol group was more active throughout their life and havedeveloped degenerative arthritis related to sport or physicalactivity more often than the colorectal cancer cases. It has beenfound that physical activity, as seen both in occupational physical activity (8) and in avocational physical activity (9), isprotective for colorectal cancer. It may be that with the greaterphysical activity, the controls are more prone to degenerativearthritis.

A previous history of "hemorrhoids" was statistically signif

icantly more common in the cases than in controls and thisapplied to both males and females. The interpretation of thesefindings is problematic, partly because the presence or absenceof hemorrhoids was not verified in any other way apart fromits being reported at the interview and partly because the word"hemorrhoids" is very loosely used for a variety of anorectal

conditions other than internal hemorrhoids among lay people.Although for the cases, the illnesses were recorded prior to theonset of the symptoms of colorectal cancer, it is possible thatfor some of the cases, what was taken by them to be a symptomof "hemorrhoids" was in fact part of the symptomatology of

their colorectal cancer. In spite of these serious problems ofinterpretation this difference is interesting and is consistentwith Burkitt's suggestion that there is an overlapping etiology

between those who have colorectal cancer and hemorrhoids,inasmuch as both groups have a low intake of dietary fiber (10).Against this finding on hemorrhoids is that there were nodifferences in other illnesses postulated by Burkitt to haveoverlapping etiologies, namely appendicitis and diverticulitis(10).

An examination of the distribution of cancers other thancolorectal cancer among cases and controls showed no statistically significant differences (Table 2). Based partly on inter-population comparisons, it has been suggested that breast cancer and cancer of the endometrium is more frequent in colorectal cancer cases than others (11), and the Melbourne data areconsistent with this view (Table 2). Of interest was the observation that in questions which relate to previous surgery whichmay have been done for a cancer, most of the "don't know"

answers were distributed among the cases (Table 2), perhapsindicating differences in recall, or possibly differences in thepersonalities of the two groups. If the hypothesis is acceptedthat those who develop cancer are often personalities who arepassive, who internalize and repress their emotions, and who

lack self-expression (12, 13), then the very high number of"don't know" answers among the cases may be interpreted as"don't want to know."

There was a statistically significant deficit of the use of aspirinand aspirin-containing compounds among cases and these dif

ferences remained statistically significant after adjustment forhypertension, heart disease, chronic arthritis, and diet in bothmales and females (Table 5). This finding, whatever the mechanism may be, has potential significance in colorectal cancerchemoprevention and merits early confirmation. Aspirin is nowwidely used in the chemoprophylaxis of cardiovascular diseaseand may also be useful in a similar way in the prevention ofcolorectal cancer and perhaps also of other cancers. There wasno statistically significant difference between cases and controlsin the previous use of oral contraceptives and this was also thefinding in two other case control studies (14, IS) and one cohortstudy (9), although in one of these there was a trend forprotection against colon cancer (14) and in another a trend forrisk of rectal cancer (15) with oral contraceptive use. The useof tranquilizers, sedatives, and sleeping pills was equally distributed among cases and controls and this was also found inanother study on breast cancer and controls (12). This is inkeeping with the finding that extreme nervousness or havinghad a nervous breakdown is similar among cases and controls(Table 1) and indicates that in the development of colorectalcancer, nervous tension and anxiety are not risk or etiologicalfactors (12).

With the exception of uterine curettage and bowel polypec-tomy, the distribution of all other operations was similar between cases and controls (Table 4). There was a statisticallysignificant deficit among cases of uterine curettage. The authorshave no hypotheses about this finding. The finding of a 6-foldrisk for colorectal cancer in those with a history of previouscolorectal polypectomy is consistent with the view that thosewith adenomatous colorectal polyps require regular surveillanceof their large bowel as a screening measure for colorectal cancer(16). There was no statistically significant association betweenprevious cholecystectomy and colorectal cancer risk in thisstudy (Table 4). While there was some evidence from earlierstudies of an association between previous cholecystectomy andright colon cancer in females, this association has probablyresulted from a bias due to confounding symptomatology, andon current evidence, it seems most unlikely that previous cholecystectomy is a risk for colorectal cancer (17,18).

REFERENCES

1. kunc. G. A., and Kune, S. The Melbourne colorectal cancer study. Adescription of the investigation, pp. 1-31. Melbourne, Australia; Universityof Melbourne, Department of Surgery Publication, 1986.

2. Kune, S. An epidemiological study of colorectal cancer, pp. 1-378. PhDDissertation, University of Melbourne, 1985. No. 8608980, pp. 1-407, AnnArbor, MI: University Microfilms International, 1986 (copyright).

3. Kune, S., Kune, G. A., and Watson, L. The Melbourne colorectal cancerstudy: incidence data on age, sex, site, migrants and religion. Int. J. Epidemici., /5: 483-493, 1986.

4. SPSS-x User's Guide. New York: McGraw-Hill Book Co., 1983.

5. Baker, R. J., and Neider, J. A. The GLIM system. Release 3. Oxford,England: Numerical Algorithm Group, 1978.

6. Adena, M. A., and Wilson, S. R. Generalised linear models in epidemiologicalresearch: case control studies. Sydney, Australia: INTSTAT Foundation,1982.

7. Kune. S., Kune, G. A., and Watson, L. F. Case-control study of dietaryetiological factors: the Melbourne colorectal cancer study. Nutr. Cancer, 9:21-42, 1987.

8. Garabrant, D. H., Peters, J. M., Mack, T. M., and Bernstein, L. Job activityand colon cancer risk. Am. J. Epidemici.. 119: 1005-1014, 1984.

9. Wu, A. H., Paganini-Hill, A., Ross, R. K., and Henderson, S. B. E. Alcohol,physical activity and other risk factors for colorectal cancer: a prospectivestudy. Br. J. Cancer, 55: 687-694, 1987.

4403




10. lim kin. D. P. Non-infective disease of the large bowel. Br. Med. Bull., 40: 14. Potter, J. D., and McMiehael, A. J. Large bowel cancer in women in relation387-389, 1984. to reproductive and hormonal factors: a case control study. J. Nati. Cancer

11. Correa, P., and Haenszel, W. The epidemiology of large bowel cancer. Adv. Inst., 71: 703-709, 1983.Cancer Res 26' 1-141 1978 '^. Weiss, N. S., Daling.J. R., and Chow, W. H. Incidence of cancer of the large12. Kune, G. A.','Bremond, A., and Bahnson, C. B. Personality and psychosocial Â£Â°welj" women â„¢"j'at'on Â¡Â°reproductive and hormonal factors. J. Nati.

factors in breast cancer patients. In: L. Dennerstein and I. Fraser (eds.), ,, ^anc" , ' * c ' . ?./ . r , , ,, j n L - Ã-oÃ-eon . j r-i â€¢/Â«.i i â€¢.i 16. Kune, G. A., Kune, S., and Watson, L. F. History of colorcctal no vpectomvHormones and Behav.our pp. 585-589. Amsterdam: Elsev,er/North-Hol- an(J risk of subsequeâ€ž;colorecta, ca'ncer. Br. j. Surg., 74: 1064-1065, 1987

land BiomÃ©dicalPress, 1986. 17 Friedman, G. D., Goldhaber, M. K., and Quesenberry, C. P., Jr. Cholecys-13. Cooper. C. L., Cooper. R. F. D., and Faragher, E. B. A prospective study of tectomy and large bowel cancer. Lancet, /: 906-908, 1987.

the relationship between breast cancer and life events, type A behaviour, 18. Kune, G. A., Kune, S., and Watson, L. F. Large bowel cancer after cholecys-social support and coping skills. Stress Med., 2: 271-277, 1986. tectomy. Am. J. Surg., in press, 1988.

4404



1988;48:4399-4404. Cancer Res Gabriel A. Kune, Susan Kune and Lyndsey F. Watson Colorectal Cancer StudyMedications: Case Control Results from the Melbourne Colorectal Cancer Risk, Chronic Illnesses, Operations, and

Updated version

http://cancerres.aacrjournals.org/content/48/15/4399

Access the most recent version of this article at:

E-mail alerts related to this article or journal.Sign up to receive free email-alerts

Subscriptions

Reprints and

[email protected] at

To order reprints of this article or to subscribe to the journal, contact the AACR Publications

Permissions

Rightslink site. Click on "Request Permissions" which will take you to the Copyright Clearance Center's (CCC)

.http://cancerres.aacrjournals.org/content/48/15/4399To request permission to re-use all or part of this article, use this link



http://cancerres.aacrjournals.org/cgi/alerts

mailto:[email protected]



colorectal cancer risk, chronic illnesses, operations, and … · ported by the "nicholas and...

Documents